Evaluating Ivonescimab as a Potential Treatment for Pleural Mesothelioma Patients Whose Cancer Has Returned After Previous Immunotherapy and Chemotherapy

NCT06840834 | Recruiting Phase 2 DMC

• 2 other identifiers: IFCT-24032024-519052-82-00
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 20

Brief Summary

Multicentre, open-label, single arm phase II study for patients with PM previously treated by immunotherapy and standard chemotherapy. 38 patients will be given second or third-line treatment with ivonescimab 20mg/kg every 3 weeks. An estimated 38 patients will be enrolled in approximately 20 centres. Patients will be treated for a maximum of 2 years, until disease progression, unacceptable toxicity, withdrawal of consent or another discontinuation criterion is met. The null hypothesis is disease control rate (DCR) at 12 weeks ≤ 30%. The alternative hypothesis is DCR ≥ 55% at 12 weeks.

Conditions

Pleural Mesotheliomas

Keywords

pleural mesothelioma; ivonescimab; bispecific antibody; anti-VEGF; anti-PD-1

Outcome Measures

Primary Outcomes (1)

• To assess the therapeutic value of the bispecific antibody anti-VEGF / anti-PD-1 ivonescimab as 2nd/3rd line treatment in relapsing PM patients

  The analysis of the primary efficacy endpoint will be conducted in all eligible patients, based on the disease control rate (DCR) at 12 weeks according to mRECIST 1.1 for mesothelioma, which was defined as the proportion of patients with compete response (CR), partial response (PR) or stable disease (SD) at 12 weeks as assessed by the independent review committtee.

  12 weeks after start of treatment.

Secondary Outcomes (5)

• Tolerance, safety of treatment

  From time of informed consent through treatment period and up to 90 days post last dose of study treatment (maximum of 2 years and 3 months).

• Progression free survival (PFS)

  At progression, up to 2 years after start of treatment.

• Overall survival

  Around 45 months.

• Best response rate

  At progression, up to 2 years after start of treatment.

• Duration of response

  At progression, up to 2 years after start of treatment.

Study Arms (1)

Ivonescimab

EXPERIMENTAL

20 mg/kg IV (a fixed dose of 3200 mg for ivonescimab should be used for patients with weight ≥160 kg), every 3 weeks.

Drug: Ivonescimab

Interventions

Ivonescimab DRUG

Ivonescimab is administered IV Q3W on Day 1 of each cycle. Ivonescimab is given at a dose of 20 mg/kg (a fixed dose of 3200 mg for ivonescimab should be used for patients ≥160 kg). The total duration of ivonescimab treatment is up to 24 months.

Also known as: SMT112

Ivonescimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed consent. Subjects must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
• Histologically-proven Pleural Mesothelioma (no cytology allowed, biopsies by thoracoscopy recommended).
• Note: pathology certification by national expert network NETMESO/MESOPATH should be checked as already done in routine in France by NETMESO regional expert MTB for PM (or similar national certification if the patient had his/her PM diagnosis obtained outside France, e.g. Belgium).
• Documented progression by CT with iodine injection according to modified RECIST 1.1 for mesothelioma (mRECIST 1.1; pleural thickness perpendicular to the chest wall or mediastinum of 7mm or more, on 2 positions, at 3 separate levels on transverse cuts of CT-scan, at least 1cm apart, the sum of 6 measurements defining a pleural unidimensional measure), or according to RECIST 1.1 for mediastinal nodes or metastatic lesion, after maximum 2 lines including immunotherapy by nivolumab ± ipilimumab, and standard P/P chemotherapy \[with (maximum 40% total of patients) or without bevacizumab\], sequentially (regardless of treatment order), or first-line combining standard chemotherapy + IO (pembrolizumab or other IO investigational drug but no anti-angiogenic drug).
• Measurable disease according to mRECIST 1.1.
• ECOG PS 0 or 1.
• Weight loss \<10% within 3 months of study entry.
• Age ≥18 years.
• Life expectancy \>3 months.
• Available pathological samples (at least 10 slides from the thoracoscopy biopsies) for centralized PD-L1, MTAP, immunohistochemistry, and NGS / transcriptome analyses, all slides being centrally reviewed by the French panel MESOPATH for mesothelioma histological certification. If archival tissue is either insufficient or unavailable, the patient may still be eligible upon discussion with IFCT.
• Adequate biological functions:
• Creatinine Clearance ≥45 mL/min (Cockroft or MDRD or CKD-epi); neutrophils
• ≥1500/mm3; platelets ≥100 000/mm3; haemoglobin ≥9 g/dL; AST and ALT \<3 x ULN, total bilirubin \<2 x ULN (patients with hepatic metastases or Gilbert's syndrome must have AST and ALT ≤5 x ULN and a baseline total bilirubin ≤2 x ULN), urine protein \<2+ or 24 hours urine protein quantification \<1.0 g, prothrombin time (PT) or international normalized ratio (INR) ≤1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless abnormalities are unrelated to coagulopathy or are secondary to prophylactic coagulation).
• Women of childbearing potential and sexually active should use a highly effective contraception method within the 28 days preceding the first dose and during the 6 months following the last dose of treatment. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.

You may not qualify if:

• ECOG PS\>1.
• Previous treatment for PM by more than 2 lines of systemic treatment, or by bevacizumab (or another anti-angiogenic / anti-VEGF pathway drug) except if combined with P/P chemotherapy \[scheme validated by ASCO, NCCN, and ESMO guidelines\] in maximum 40% of the total of recruited patients (n=15).
• Suspicion of hyperprogressive disease or rapid tumour progression when treated by previous IO (i.e. progressive disease within 9 weeks of treatment by previous nivolumab ± ipilimumab or alternative immunotherapy, starting from C1D1 or from randomization if previous experimental immunotherapy).
• Pleural effusion as the only radiological abnormality without measurable pleural thickness or mediastinal node enlargement.
• Peritoneal, pericardial or tunica vaginalis testis mesothelioma, without any pleural involvement at the time of diagnosis.
• Previous diagnosis of adenocarcinoma from any anatomic site within the previous 3 years, with the exception of prostate adenocarcinoma history in case of localized prostate cancer with good prognostic factors according to d'Amico classification (\<T2a, Gleason score ≤6 and PSA ≤10 ng/ml), provided they were treated in a curative modality (surgery or radiotherapy, without any chemotherapy).
• Previous or active cancer within the previous 3 years (except for already treated in situ carcinoma of the cervix, or basal cell skin cancer, treated or not).
• Uncontrolled pleural effusion despite previous (talc or other) pleurodesis, requiring thoracocentesis (by pleural aspiration) more often than every 21 days. However, patients with efficient indwelling pleural catheter (IPC) are eligible.
• Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 2 weeks delay between the end of radiotherapy and the beginning of the treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids (\>10 mg prednisone equivalent daily) or mannitol infusions, are allowed.
• Radiotherapy needed at initiation of treatment, except bone palliative radiotherapy on a painful or compressive tumour site (in this case, target lesions should not be selected in the irradiated zone).
• History of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before registration date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment for any kind of disease.
• Systemic treatment with corticosteroids with a dose \>10 mg prednisone equivalent daily, within 14 days before initiation of the treatment. Inhaled, nasal or topical corticosteroids are allowed.
• History of active autoimmune disease, needing systemic immunosuppressive drug, including but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with anti-phospholipid syndrome, Sjogren's syndrome with interstitial pulmonary disease, Guillain-Barré syndrome within previous 15 years, multiple sclerosis, vasculitis, or glomerulonephritis.
• Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) or benign rheumatoid polyarthritis not needing any immunosuppressive systemic treatment or \>10 mg daily oral steroids, or benign sicca syndrome (Sjogren) without interstitial lung disease (ILD), or history of past Guillain-Barre syndrome beyond 15 previous years, totally reversible with no sequelae, no systemic immunosuppressive treatment during the last 20 years, are allowed to be included. Patients with Grave's disease or psoriasis not requiring systemic therapy within the previous two years from are allowed to be included.
• Active inflammatory intestinal disease (diverticulosis, Crohn's disease, haemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhoea.

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead
• Summit Therapeutics: collaborator

Study Sites (20)

Besançon - CHU

Besançon, France

RECRUITING

Brest - CHU

Brest, France

RECRUITING

Caen - CHU

Caen, France

RECRUITING

Clermont-Ferrand - Centre Jean Perrin

Clermont-Ferrand, France

RECRUITING

Créteil - CHI

Créteil, France

RECRUITING

Grenoble - CHU

Grenoble, France

RECRUITING

Le Mans - CHG

Le Mans, France

RECRUITING

Lille - CHU

Lille, France

RECRUITING

Marseille - APHM

Marseille, France

RECRUITING

Montpellier - CHU

Montpellier, France

RECRUITING

Mulhouse - GHRMSA

Mulhouse, France

RECRUITING

Nantes - Hôpital Laennec

Nantes, France

RECRUITING

Paris - Bichat

Paris, France

RECRUITING

Bordeaux - CHU

Pessac, France

RECRUITING

Lyon - HCL

Pierre-Bénite, France

RECRUITING

Strasbourg - Nouvel Hôpital Civil

Strasbourg, France

RECRUITING

Toulon - CHI

Toulon, France

RECRUITING

Toulouse - CHU

Toulouse, France

RECRUITING

Tours - CHU

Tours, France

RECRUITING

Metz - Hôpital Robert Schuman

Vantoux, France

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Mesothelioma, Malignant

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

IFCT

CONTACT

+33 156811046; contact@ifct.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2025
• First Posted: February 21, 2025
• Study Start: June 30, 2025
• Primary Completion: March 24, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 16, 2026

Record last verified: 2025-09

Locations

FR (20)